The lungs are kept from collapsing by a material called surfactant, which is produced and secreted into the airspaces of the lung by one of the cell types which line the airspaces, type II alveolar epithelial cells. Abnormal production, secretion or reuptake of surfactant by type II cells results in diseases such as pulmonary alveolar proteinosis and infant respiratory distress syndrome. Despite the clinical importance of surfactant, little is known about the regulatory mechanisms involved. In the past decade, technical advances have been made which make this proposal possible. First, techniques for isolating and culturing type II cells now permit reliable in vitro studies of surfactant metabolism. Second, the patch clamp technique has enabled electrical recording from small cells such as type II cells. In this project, these techniques will be applied together to characterize the ion channels in rat type II cells, and to determine their role in the production and secretion of surfactant. The patch clamp technique will be used to discover what types of ion channels are present in the plasma membranes of type II cells, to determine the properties of these ion channels, and the numbers of ion channels per cell. Several approaches will be taken to learn what physiological functions the ion channels perform. (1) Comparing the ion channels in type II cells actively secreting surfactant with those in cells that are not may provide clues to which ion channels are involved. (2) Drugs and physiological modulators of surfactant production and secretion will be tested for possible effects on ion channels. (3) Specific ion channel blocking agents will be tested to see whether blocking a given ion channel inhibits surfactant production or secretion. The knowledge gained from this project may eventually enable rational pharmacological intervention in disease conditions exhibiting abnormal surfactant turnover.